Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)

NCT01230580 | Unknown Phase 4 DMC

• 2 other identifiers: PIVOT2007-006448-23
• Study Type: interventional
• Target: 587
• Locations: 0 countries
• Sites: N/A

Brief Summary

The PIVOT trial aims to determine whether a strategy of switching to PI monotherapy is non-inferior to continuing triple-therapy, in terms of the proportion of patients who maintain all the drug treatment options that were available to them at baseline after at least 3 years of follow-up, and to compare clinical events, safety, toxicity and health economic parameters between the two strategies.

Conditions

HIV Infection; Acquired Immunodeficiency Syndrome

Keywords

Protease Inhibitors; RNA virus infections; Virus diseases; Sexually Transmitted Diseases viral; Immune system diseases; Anti-infective Agents; Drug resistance

Outcome Measures

Primary Outcomes (1)

• Loss of future drug options

  The first occurrence of intermediate to high level resistance to any one or more of the standard antiretroviral drugs (limited to licensed drugs in contemporary use) to which the patient's virus was considered to be sensitive at trial entry (i.e. excluding drug resistance that was known to be present on previous resistance testing).

  Up to 5 years

Secondary Outcomes (12)

• Death from any cause

  Up to 5 years

• Serious AIDS-defining illness

  Up to 5 years

• Serious non-AIDS defining illness

  Up to 5 years

• Adverse events

  Up to 5 years

• Confirmed Virological rebound

  Up to 5 years

Study Arms (2)

Protease Inhibitor Monotherapy

EXPERIMENTAL

Ritonavir-boosted protease inhibitor

Drug: Protease Inhibitor

Control

ACTIVE COMPARATOR

Standard-of-care triple-therapy regimen

Drug: Standard-of-care Antiretroviral therapy

Interventions

Protease Inhibitor DRUG

Switch to a regimen comprising a single ritonavir-boosted Protease Inhibitor

Protease Inhibitor Monotherapy

Standard-of-care Antiretroviral therapy DRUG

Regimen should consist of 3 drugs: 2 nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Vl \< 50 for 24 weeks prior to screening CD4 \> 100 at screening

You may not qualify if:

• Known major protease resistance mutation(s) documented on prior resistance testing if performed (prior resistance testing is not mandatory for trial participation).
• Previous change in ART drug regimen for reasons of unsatisfactory virological response (patients who have changed regimen for prevention or management of toxicity or to improve regimen convenience are permitted to enter the trial).
• Previous allergic reaction to a PI.
• Patient currently using or likely to require use of concomitant medication with known interaction with PIs.
• Patient requiring treatment with radiotherapy, cytotoxic chemotherapy, or is anticipated to need these during the trial period.
• Treatment for acute opportunistic infection within 3 months prior to trial screening.
• Pregnant or trying to become pregnant at the time of trial entry.
• History of active substance abuse or psychiatric illness that, in the opinion of the investigator, would preclude compliance with the protocol, dosing schedule or assessments.
• History of HIV encephalopathy with current deficit \>1 in any domain of the Neuropsychiatric AIDS Rating Scale (see Appendix 7).
• Past or current history of cardiovascular disease, or 10 year absolute coronary heart disease risk of \>30%, or risk of \>20% if the patient has diabetes or a family history of premature ischaemic heart disease or stroke.
• History of insulin-dependent diabetes mellitus.
• Patient currently receiving interferon therapy for Hepatitis C virus infection or planning to start treatment for Hepatitis C at the time of trial entry.
• Co-infection with hepatitis B, defined as Hepatitis BsAg positive at screening or at any time since HIV diagnosis, unless the patient has had a documented Hepatitis B DNA measurement of less than 1000 copies/ml taken whilst off Hepatitis B active drugs.
• Any other active clinically significant condition, or findings during screening medical history or examination, or abnormality on screening laboratory blood tests that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
• Fasting plasma glucose \>7.0mmol/L at trial screening.

Sponsors & Collaborators

• Medical Research Council: lead
• NHS Health Technology Assessment Programme: collaborator

Related Publications (1)

• Winston A, Arenas-Pinto A, Stohr W, Fisher M, Orkin CM, Aderogba K, De Burgh-Thomas A, O'Farrell N, Lacey CJ, Leen C, Dunn D, Paton NI; PIVOT Trial Team. Neurocognitive function in HIV infected patients on antiretroviral therapy. PLoS One. 2013 Apr 30;8(4):e61949. doi: 10.1371/journal.pone.0061949. Print 2013.

  PMID: 23646111 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Immune System Diseases

Interventions

Protease Inhibitors

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Slow Virus Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Nick Paton, MD

  Medical Research Council

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: October 27, 2010
• First Posted: October 29, 2010
• Study Start: November 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: October 10, 2012

Record last verified: 2010-10